Hepatitis C (HCV) is common among substance abuse experienced patients, causes significant morbidity and mortality, and while effective treatment is available, relatively few initiate and complete therapy. Treatment for HCV in both mono and HCV/HIV co-infected patients is a long and difficult course, involving 6 to 12 months of Peg-lnterferon injections and oral Ribavirin (PEG-IFN/RBV). Over 40% of patients develop depression due to the medication, which in turn leads to discontinuation and lost opportunities to prevent liver disease. Cognitive Behavioral Therapy (CBT) is a well-established modality shown to be as effective, or more effective, than antidepressant medications in treating depression and is associated with a lower risk of relapse. CBT is also effective in treating depression due to medical disease and preventing depression in high-risk individuals. As a non-pharmacologic therapy, CBT may be superior to antidepressant drugs in HCV by minimizing side effects, and drug-disease and drug-drug interactions. The cognitive skills CBT teaches may also help bolster adherence with HCV and HIV regimens. While CBT prior to and during PEG-IFN/RBV treatment of non-depressed HCV patients is a promising, non-pharmacological method for safely reducing rates of depression and increasing adherence with treatment, its efficacy in this setting is unknown. The purpose of this study is to develop, refine, and evaluate the initial efficacy of pilot CBT intervention in mono-infected/co-infected, non-depressed patients with substance abuse experience being treated with PEG-IFN/RBV. Our specific aims are to perform a pilot RCT to compare the effect of CBT to: 1) Develop refine and test feasibility of a program of group CBT 2)reduce the rate of depression that occurs during treatment, 3) increase the number of patients completing HCV treatment. We will randomize 60 inner city, mono and co-infected HCV patients with substance abuse experience planning treatment with PEG-IFN/RBV to our new CBT intervention or usual care supplemented by support group. Of these 60 patients, 20 mono- infected and 20 co-infected individuals will receive CBT, and 20 will receive control support group. The intervention will have 8 group sessions (2 hours each) led by a trained CBT therapist. Three sessions will occur in the 2 months before starting PEG-IFN/RBV. The remaining 5 sessions will be monthly during the first 6 months of treatment. Patients will complete the Beck Depression Inventory and other validated instruments at baseline, 3 and 6 months. The results of this feasibility study will be used to further refine the CBT modules and design a large, fully-powered randomized controlled trial to definitively assess its efficacy in preventing PEG-IFN/RBV associated depression and improving HCV treatment completion rates among vulnerable populations. [unreadable] [unreadable] [unreadable] [unreadable]